Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Contribution of cosmetic ingredients and skin care textures to emotions.

OBJECTIVE: Emotions play an important role in consumers' perception of a sensory experience. The objective of this work was to investigate the ability of basic skin care formulas (i.e. without interference of odour, colour and packaging) and pillar ingredients (i.e. emollients and rheology modifiers) to elicit emotions. Another objective was to track, as claimed by neurocosmetics, the possible effect of formulas to trigger emotions from their direct biochemical effects on the skin. METHODS: Standard methodologies were mobilized, combining subjective and behavioural parameters (i.e. verbatim, prosody and gesture). Sense and Story methodology based on a collection of metaphoric verbatim was conducted after an induction phase. In addition, an experimental electrophysiological real-time visualization method was tried as a first experience in cosmetics. Finally, the ability of formulations with emotional benefits to modulate the release of neuropeptides by sensory neurons was evaluated on a 3D human model (epidermis co-cultured with sensory neurons). RESULTS: Skin care formulas were shown to play a role in emotional potential and the types of emotion generated, while changing one ingredient mostly acted on the intensity of the emotions. Verbatim provided contrasted answers depending on the protocol, highlighting the interest of non-verbal approaches to detect subtle effects. The in vitro model substantiated physiological effects of skin care formulas with emotional potential on human skin sensory neuron activity. CONCLUSION: Emotions were impacted by the change in ingredients and were better captured through non-verbal methods.

OBJECTIF: Les émotions jouent un rôle important dans la perception qu'ont les consommateurs d'une expérience sensorielle. L'objectif de ce travail était d'étudier la capacité de formules de soins pour la peau de base (c'est­à­dire sans interférence d'odeur, de couleur, d'emballage) et d' ingrédients essentiels (c'est­à­dire les émollients et les modificateurs de rhéologie) à susciter des émotions. Un autre objectif était de suivre, comme le prétendent les neurocosmétiques, l'effet possible des formules à déclencher des émotions à partir de leurs effets biochimiques directs sur la peau. MÉTHODES: Des méthodologies standards ont été mises en œuvre, combinant des paramètres subjectifs et comportementaux (c'est­à­dire verbatim, prosodie et gestuelle). La méthodologie Sense & Story basée sur un ensemble de verbatim métaphoriques a été mise en œuvre après une phase d'induction. En outre, une méthode expérimentale de visualisation électrophysiologique en temps réel a été testée comme première expérience dans le domaine des cosmétiques. Enfin, la capacité des formulations présentant des bénéfices émotionnels à moduler la libération de neuropeptides par les neurones sensoriels a été évaluée sur un modèle humain 3D (épiderme co­cultivé avec des neurones sensoriels). RÉSULTATS: Il a été démontré que les formules de soins pour la peau jouent un rôle dans le potentiel émotionnel et les types d'émotions générées, tandis que le changement d'un ingrédient agit principalement sur l'intensité des émotions. Le verbatim a fourni des réponses contrastées selon le protocole, soulignant l'intérêt des approches non verbales pour détecter les effets subtils. Le modèle in vitro a confirmé les effets physiologiques des formules de soins pour la peau ayant un potentiel émotionnel sur l'activité des neurones sensoriels de la peau humaine. CONCLUSION: Les émotions ont été affectées par le changement d'ingrédients et ont été mieux saisies par des méthodes non verbales.

Effect of the supplementation of virgin coriander seed oil on reducing reactivity in healthy women with sensitive skin: a randomized double-blind placebo-controlled pilot clinical study.

Sensitive skin is a common condition that affects many people in the world, especially women. This syndrome is defined by the occurrence of unpleasant sensations such as stinging and burning in response to stimuli that should not normally provoke such sensations. Coriander seed oil (CSO) is a 100% virgin oil of coriander seeds and boasts a specific composition of fatty acids, mainly petroselinic acid (60-75%). It has demonstrated its ability to regulate inflammation (NF-κB pathway) and nociception (TRPA1 pathway), two mechanisms supporting sensitive skin, in previous in vitro research. It was, therefore, a good candidate to be tested in vivo on sensitive skin conditions. A pilot clinical study was conducted to evaluate the effect of this ingredient on healthy women showing excessive skin reactions, mainly redness and discomfort when subjected to external stress. The results showed that the daily consumption of 200 mg of CSO for 28 days effectively reduced redness induced by stripping stress and itching induced by stinging stress. It also improved the perception of skin sensitivity and reactivity after 56 days of consumption. These clinical results confirmed that CSO is a promising ingredient to contribute to reducing reactivity in sensitive skin.

In vitro testing strategy for assessing the skin sensitizing potential of "difficult to test" cosmetic ingredients.

Before placing a new cosmetic ingredient on the market, manufacturers must establish its safety profile, in particular assessing the skin sensitization potential, which is a mandatory requirement for topical applications. Since the ban on animal testing in Europe, and its extension to many parts of the world, a battery of in vitro tests covering the key steps of the Adverse Outcome Pathway (AOP) for skin sensitization is recommended. To date, three in vitro methods are validated in the OECD guidelines (442C, 442D, 442E), and many others are under validation by OECD (2019) and ECVAM. However, there is still no official strategy. Some industrial manufacturers have proposed in vitro strategies with good predictivity, but their studies were mainly based on the testing of simple and "easy to test" substances. This work therefore focused on "difficult to test" ingredients with particular physicochemical properties (i.e. poorly water-soluble components) or with particular intrinsic properties placing them outside the applicability domains of most in vitro models (irritants or cytotoxic like surfactants, complex substances). Furthermore a particular focus was made on weak to moderate sensitizers. The objective was to develop a robust, quick and straightforward testing strategy enabling the evaluation of the skin sensitization potential of "difficult to test" ingredients. In this context, four in vitro test models were used: three validated methods and the Sens-Is® assay, currently in the work plan of the OECD, chosen for its ability to overcome solubility issues and to discriminate irritants from sensitizers. 25 ingredients with particular physicochemical properties were evaluated, chosen among positive or negative sensitizers according to in vivo data (M&K and/or LLNA). Such ingredients, including cleansers, solubilizers, emulsifiers, emollients, active ingredients, preservatives, and antioxidants are indeed essential constituents of cosmetic and dermopharmaceutical formulations. The results analysis on each in vitro test demonstrated that the DPRA model was the less predictive on the chosen ingredients, resulting especially in many false negative responses compared to animal studies, or being unsuited to the mode of action of the selected ingredients. On the contrary, the Sens-Is® assay revealed a real capability to discriminate sensitizers from non-sensitizers. The two other models, KeratinoSensTM and h-CLAT, showed a lower ability to classify the materials correctly than in previously published studies, linked to the particular physicochemical and intrinsic properties of the chosen ingredients and the applicability domains of these in vitro tests. The KeratinoSensTM model tended to overestimate the sensitization potential of the tested ingredients, whereas the h-CLAT model tended to underestimate the sensitizers. Based on these results a new sequential testing strategy was set up combining 1 to 3 models to cover the main key events of the skin sensitization AOP. Sens-Is® model, assessing the first two AOP Key Events with consideration of the ingredient dermal penetration, is chosen as a starting point. The approach is completed, depending on the first response, by the h-CLAT model, assessing Key Event 3, and then potentially KeratinoSensTM assessing Key Event 2, but with a more direct application mode. This new testing strategy increases the accuracy to 88% on the selected ingredients and minimizes the risk of a false negative conclusion, which is crucial from the perspective of the ingredients' users and cosmetic consumers.